Glycoprotein peptide of the human herpesvirus-7 for use in particular in an elisa serologic test

ABSTRACT

The invention concerns an immunogenic peptide comprising at least six consecutive amino acids of a hydrophilic region of the glycoprotein B (gB) of the human herpesvirus-7 (HIV-7), and reacting specifically with antibodies directed against HHV-7, and diagnosis kit containing it.

[0001] The present invention relates to peptides from the glycoprotein Bfrom human herpesvirus 7 (HHV-7), which can be used to carry out aserological test that is specific for HHV-7, or in pharmaceuticalcompositions intended to stimulate an immune response directed againstHHV-7.

[0002] Human herpesvirus 7 is a β-herpesvirus (virus with a DNAenvelope) discovered in 1990. The virus is widespread in the generalpopulation and produces a primary phase infection early in life and,like other herpesviruses, persists indefinitely in the latent form inthe infected organism. HHV-7 is genetically close to cytomegalovirus(CMV) and to human herpesvirus 6 (HHV-6) which, especially in the caseof CMV, are major pathogenic viruses. The responsibility of HHV-7 forhuman diseases appears to be modest from current knowledge, but itspathogenic power is far from having been explored completely. It isfeared that, during immunodepression, its pathogenic power isexacerbated and gives rise to serious opportunistic infections, likeother herpesviruses. In particular, this may be the case after organtransplant. The reactivation of HHV-7 may be pathogenic and mayaggravate the immunodepressed condition because of the selective tropismof HHV-7 for T CD4+ lymphocytes.

[0003] Further, molecules that are active against CMV and already widelyused in medical therapy (foscamet, cidofovir, ganciclovir) are activeagainst HHV-7. A priori, the existence of active treatments furtherunderlines the importance of continuing studies on the detection ofinfections using that virus.

[0004] There is currently no completely satisfactory means on the marketfor the specific diagnosis of a chronic infection by HHV-7. Methods forthe specific diagnosis of an infection by HHV-7 based on amplifying aportion of the viral genome by PCR using specific primers for HHV-7 havebeen described, for example in International patent applicationWO-A-97/03345. However, such methods lack sensitivity for diagnosing achronic infection and are thus destined to detect (and possiblyquantify) an active infection.

[0005] Detection of a chronic infection necessitates a serological test,which will reveal the presence or otherwise of anti-HHV-7 antibodies inthe sample. Current commercially available serodiagnostic HHV-7 systemsare not completely satisfactory. HHV-7 diagnosis is currently carriedout using cells infected with HHV-7 as the antigen. However, the geneticproximity of other β-herpesviruses, in particular HHV-6, deleteriouslyaffects the specificity of that type of test. Adsorption tests onantigens from cells infected with the other viruses are necessary toenhance the specificity of said tests.

[0006] Thus, determination of antigenic molecules that are genuinelyspecific to HHV-7 represents a significant advance in the development ofa serological test that is specific for this virus and easy to carryout.

[0007] In this context, Secchiero et al described antigens for a HHV-7protein, pp85 (WO-A-99/02554). Certain of said antigens appear to bespecific to HHV-7.

[0008] However, protein pp85, coded for by the U14 gene, is a tegumentphosphoprotein for which a lower specificity than that carried by theglycoproteins of the viral envelope can be expected. Further, although aspecific epitope has been localized in the C-terminal portion of theprotein, the peptides carrying that epitope could not be used toestablish a functional ELISA test (Stefan et al, J Clin Microbiol 1999;37: 3980-5), which remains the prime objective of HHV-7 serology.Finally, in terms of immune protection, it is conventionally recognizedthat the glycoproteins of the viral envelope, and in particular gB, area better target for neutralizing antibodies than tegument proteins.

[0009] The present invention concerns peptides from HHV-7 glycoprotein B(gB).

[0010] HHV-7 gB, present on the surface of infected cells and virions,is involved in attachment and fusion of the virus to the cell surface.By analogy with the other herpesviruses, it was supposed that gB wasimmunogenic, giving rise to neutralizing antibodies and a cellularimmune response in infected subjects. All of the results published sofar corroborate this hypothesis, even though gB, an indispensableprotein of the virus, doe not appear to be like the immunodominantprotein as regards the reactivity of the human seric antibodies incurrent immunoblot tests.

[0011] The first part of the study of gB consisted of amplifying thegene for gB using a polymerase chain reaction (PCR) and analyzing thecorresponding PCR products in more than 100 subjects. This study showedthat the gene for gB was very stable (Franti et al, 1998 and 1999). Thisdata agrees with a comparison of two distinct strains of HHV-7 thecomplete sequence of which has been published (Nicholas, 1996; Megaw etal, 1998): the nucleotide divergence between the two strains is of theorder of 0.1%. However, a determination of the partial nucleotidesequence for gB in many individuals has demonstrated five critical basesubstitution sites with no modification to the polypeptide sequence and6 distinct combinations of said sequences, alleles, have been described.Said alleles are very important as epidemiological markers, but theirdescription does not cause the perfect conservation of the gB as a viralprotein among all of the strains tested to be re-examined. This propertyconstitutes a good candidate for defining antigenic reagents that canreact with antibodies directed against any viral HHV-7 strain incirculation.

[0012] The present invention results from cloning the entire gene for gBand its expression in a prokaryotic expression system, colibacillus.Further, the entire gene and the N-terminal portion have been cloned andexpressed in a eukaryotic expression system, baculovirus. Stableexpression has been obtained in bacteria, as well as stable expressionwith cleavage of the precursor protein in the baculovirus system.Expression at the surface of SF21 insect cells infected with recombinantbaculoviruses appears to be close to that of natural gB. This productionof recombinant protein, after transfer of the protein to anitrocellulose membrane, has allowed the reactivity of a battery ofeight different human serums seropositive for HHV-7 to be tested using aWestern blot technique.

[0013] A first series of experiments led to the following conclusions:(i) specific antibodies directed against the recombinant gB exist in theeight serums tested; (ii) the reactivity of the antibodies directedagainst said surface glycoprotein is directed against the N-terminalportion of the gB which produces the same reaction profile as the entireprotein. This confirms the hypothesis that gB induces antibodies ininfected subjects and that partial forms of recombinant gB, allow saidantibodies to be detected. However, the results are spoiled by thepresence of unwanted bands, probably related to non specific reactivityphenomena, and the Western blot technique is not really suitable tolarge scale use.

[0014] In order to overcome these problems, the authors of the presentinvention undertook to define and synthesize a peptide localized in theN-terminal region of gB. Said peptide had to have the following twocharacteristics: (i) the peptide must be derived from a highlyhydrophilic region of gB, which can interact with an antibody; (ii) thepeptide must have a very low homology with the gB of the two other humanβ-herpesviruses, HHV-6 (which includes two variants, HHV-6A and HHV-6B)and CMV, to avoid cross serological reactions. The spotlight fell on apeptide containing 24 amino acids, corresponding to amino acids 129-152of gB, located in the N-terminal region and defined by the peptidesequence:

[0015] Peptide H7GB 129-152

[0016]Leu-Ser-Ser-Ile-Ser-Val-Lys-Arg-Ser-Glu-Glu-Glu-Glu-Tyr-Val-Ala-Tyr-His-Lys-Asp-Glu-Tyr-Val-Asn(LSSISVKRSEEEEYVAYHKDEYVN).

[0017] Reference should now be made to FIGS. 1 to 3 in order to defineand identify the selection of the peptide in the protein.

[0018]FIG. 1 shows the hydrophilicity curves for HHV-7 gB (1A), HHV-6A(1B), HHV-6B (1C) and CMV (1D), on which the region corresponding to theregion exposed to HHV-7 gB is indicated by an arrow and the H7GB 129-152peptide is shown as a black line.

[0019]FIG. 2 shows a higher resolution study of the hydrophilicity ofthe selected region, the H7GB 129-152 peptide being shown as the blackline.

[0020]FIG. 3 shows the alignment of the protein sequences of the gB ofHHV-7, HHV-6A, HHV-6B and CMV, in the region of the H7GB 129-152 peptide(shown on the first line).

[0021] This region of 24 amino acids offers the advantage of being inthe N-terminal quarter of the protein and thus of being exposed to theoutside of the molecule because of its hydrophilicity. This exposedregion is found in the position that is substantially homogeneous withthe other β-herpesviruses (HHV-6A, HHV-6B, CMV) (FIG. 1).

[0022] A higher resolution study of the hydrophilicity of the selectedregion shows, however, after alignment of the sequences, that thehydrophilicity peak of HHV-7 does not occupy exactly the same positionas those of HHV-6A, HHV-6B, and CMV (FIG. 2). A study of the proteinsequence, again after alignment (FIG. 3), confirms that HHV-7 has ahighly hydrophilic original sequence centred on residues 136-141 in theselected region of the peptide:

[0023] Arg-Ser-Glu-Glu-Glu-Glu (RSEEEE).

[0024] This sequence is not found in other β herpesviruses. In orderthat this motif, which most probably represents all or a portion of thedominant epitope or epitopes, is present and correct after adsorptiononto a solid support, bordering sequences have been joined to saidparticular sequence to produce the total sequence of the above H7GB129-152 peptide.

[0025] It should be noted that this peptide contains, at its C-terminalend, a motif Asp-Glu-Tyr-Val-Asn, which is a priori highly hydrophilic,which can also behave as an epitope as regards anti-gB antibodies.However, it is improbable that this region at the free end of thepeptide could adopt a configuration conducive to behaving as a linearepitope. Further, the Asn terminal residue can be a gB N-glycosylationsite as it belongs to a canonical sequence Asn-X-Thr which is wellconserved in the four β-herpesviruses. The steric hindrance caused byglycosylation (if it exists) probably would oppose exposure of theAsp-Glu-Tyr-Val-Asn motif as an epitope on the surface of the molecule.

[0026] Thus, the present invention concerns immunogenic peptidescomprising at least six consecutive amino acids from a hydrophilicregion of the glycoprotein B (gB) of human herpesvirus 7 (HHV-7) andreacting in a specific manner with antibodies directed against HHV-7.The term “reacting specifically with antibodies directed against HHV-7”means that antibodies directed against β-herpesviruses other than HHV-7(for example against HHV-6) do not have a particular affinity for saidpeptides.

[0027] Preferably, the amino acids sequence of the gB present in thepeptides of the invention derive from the N-terminal region of saidprotein.

[0028] In a preferred implementation of the peptides of the invention,their sequence comprises the motif Arg-Ser-Glu-Glu-Glu-Glu. Morepreferably, a peptide of the invention is characterized in that itcomprises the sequence Ser-Val-Lys-Arg-Ser-Glu-Glu-Glu-Glu-Tyr-Val-Ala,if necessary modified by one of more amino acid substitutions. Anymodifications to said sequence will be made so that the presentation ofthe motif Arg-Ser-Glu-Glu-Glu-Glu will always permit its interactionwith anti-HHV-7 antibodies. In particular, the amino acids can besubstituted with amino acids with an analogous hydrophilicity.

[0029] The peptides of the invention preferably comprise 15 to 25 aminoacids, but this is not limiting in nature.

[0030] A particular peptide of the invention is the H7GB 129-152 peptidecorresponding to amino acids 129 to 152 of gB and defined by the peptidesequence:Leu-Ser-Ser-Ile-Ser-Val-Lys-Arg-Ser-Glu-Glu-Glu-Glu-Tyr-Val-Ala-Tyr-His-Lys-Asp-Glu-Tyr-Val-Asn.If appropriate, the sequence for said peptide can be modified by one ormore conservative amino acid modifications, provided that theimmunological reactivity of said peptide is not modified.

[0031] The peptides of the invention as described above can also bemodified by adding one or more terminal amino acids that areheterologous to gB to one end or to both ends. If appropriate, saidpeptides can also be labeled.

[0032] The eight human serums tested as described above by Western blotwere used to determine the best reactivity conditions for said peptidein an ELISA system (Example 1 below). The following can be defined(optical density):

[0033] mean value of the background noise to the reaction: 0.09;

[0034] mean value of the results obtained with negative serums: 0.18;

[0035] a positivity threshold of 0.23, corresponding to the mean ofnegatives increased by 2 standard deviations (error risk of 5%) or 0.25,corresponding to the mean of negatives increased by 3 standarddeviations (error risk of less than 1%);

[0036] a spectrum of positive serum values of 0.4 to 1.1.

[0037] The reproducibility of the results was shown to be highlysatisfactory, both when comparing separate experiments carried outsimultaneously (intra-test variability study) and with separateexperiments carried out on different days (inter-test variabilitystudy). The specificity of the results as regards the peptide used wasverified in several ways:

[0038] test for positive HHV-7 serums towards a further non pertinentviral peptide (HHV-8 peptide) under the same conditions or in theabsence of any peptide fixed in the reaction wells: the reactions arealways under the positivity threshold (Example 2 below);

[0039] test for positive HHV-7 serums towards a HHV-7 peptide afteradsorbing the serums on different extracts from infected cells: thepositivity signal is significant reduced or even disappears when cellsare infected with HHV-7 but conserved or only slightly modified when thecells are infected with CMV and HHV-6 (Example 3 below);

[0040] absence of reactivity with six seronegative HHV-7 serums (Example4 below);

[0041] inhibiting action of soluble peptide brought into contact inadvance with serums, on ELISA reactivity by a dose-dependent competitionphenomenon (Example 5 below).

[0042] It should be noted that the present invention is not in any caselimited to the H7GB 129-152 peptide described above. In contrast, anypeptide comprising a region that is homologous with the HHV-7 gB proteinand which has immunological properties similar to those of H7GB 129-152(i.e., reacting in a specific manner with antibodies directed againstHHV-7), is also encompassed in the scope of the present invention. Meansfor determining whether a peptide falls within the scope of the presentinvention are described in the examples.

[0043] In particular, a peptide carrying the residuesArg-Ser-Glu-Glu-Glu-Glu, surrounded by amino acids that are partially ortotally heterologous to gB, can react specifically with antibodiesdirected against HHV-7, provided that they are correctly presented. Theinfluence of inserting or deleting residues surrounding theArg-Ser-Glu-Glu-Glu-Glu motif on the immunological properties of thepeptide obtained are difficult to predict if the total charge of thepeptide and the polarity of the modified residues are conserved overall.In all cases, only synthesis of a novel peptide and its testing (forexample, by ELISA as described in Example 1) will allow the functionaleffect of any modifications to be accurately determined.

[0044] The properties of the peptides of the invention thus allow themto act as a basis for the development of a specific serological test theindications for which should be, inter alia:

[0045] monitoring and studying HHV-7 infections in children at the timeof primary phase infection (1-3 years);

[0046] serological monitoring of immunodepressed subjects with the ideaof correlating modifications to the serological reactivity to the degreeof dysfunction of the immune system;

[0047] demonstrating a correlation between the titer of the anti-gBantibodies and the capacity to control HHV-7 infection;

[0048] a clear distinction between HHV-7 and HHV-6 infections fromcertain particular clinical manifestations connected with primary phaseinfection and in general seroprevalance studies;

[0049] determining the HHV-7 serology of a candidate for an organ graftand a potential organ donor for use in grafts.

[0050] The present invention also concerns a kit for the specificdiagnosis of HHV-7, comprising a peptide as described above. Ifappropriate, said peptide can be fixed on a support. Preferably, adiagnostic kit of the invention also comprises a detectable antibodydirected against one or more classes of human immunoglobulins. Thisdetectable antibody may be radio-labelled, fluorescent, or bound to anenzyme. In the case in which the detectable antibody is bound to anenzyme, the kit advantageously comprises a substrate for said enzymewhich allows a visually detectable result to be produced.

[0051] The peptides of the invention can also be used in the compositionof more complex diagnostic kits which, in addition to specificallydetecting an HHV-7 infection, enable serodiagnosis of a sample asregards one or more other β-herpesviruses to be carried out.

[0052] The invention also provides a method for serological detection ofHHV-7 in a biological sample, comprising a step for bringing saidbiological sample into contact with a peptide as hereinbefore described,and a step for determining bonding of the peptide with any antibodiesthat may be present in the sample. In such a method, the step fordetermining bonding of the peptide with any antibodies that may bepresent in the sample can be carried out using any method that isaccessible to the skilled person for identifying a specific bond betweenan antigen and an antibody, in particular using an ELISA test,chemiluminescence, by fixing onto a micro- or macro-array type support,by immunofluorescence, by radio-immuno-labelling, by agglutination or byhaemagglutination.

[0053] Further, the immunological properties of the peptides describedabove constitute particularly interesting candidates for forming part ofthe composition of immunogenic preparations intended to encourage animmune response against HHV-7 in a subject. Said preparations can becomplex and may comprise other antigens, in particular the majorantigens of HHV-7 or possibly of other β-herpesviruses. The inventionthus also concerns an immunogenic preparation intended to encourage animmune response against HHV-7, characterized in that it comprises atleast one peptide at least one region of which derives from gB, asdescribed above.

[0054] Finally, the invention concerns the use of a peptide inaccordance with the invention in preparing a pharmaceutical compositionfor the serological detection of HHV-7, the diagnosis of HHV-7 in asubject, or stimulation of an immune response directed against HHV-7 ina subject.

[0055] The following examples and figures provide non-limitingillustrations of certain advantages and features of the presentinvention.

EXAMPLE 1 Determination of Optimum Conditions for the Reactivity of theH7GB 129-152 Peptide in an ELISA System

[0056] A variety of concentrations of peptide (0.1 to 5 μg/ml) were usedwhen fixing to the bottom of reaction wells, along with differentdilutions of human serum during an ELISA test. The conditions judged tobe the best were a peptide concentration of 0.5 μg/ml and a serumdilution of {fraction (1/100)}. However, other conditions, includingmodifications to the other reagents, could result in better performingtests.

EXAMPLE 2 Test for Positive HHV-7 Serums Towards Another Non-PertinentViral Peptide (HHV-8 Peptide) in an ELISA System with the H7GB 129-152Peptide

[0057] Eight reference serums seropositive for HHV-7, labeled P1 to P8,were tested in the absence of the peptide and against a HHV-8 peptidethat had no homology with H7GB 129-152. The results (summarized in thetable below) of the optical density indicate an absence of a significantreactivity under these conditions (positivity threshold for the reactioncorresponded to an OD of 0.25). peptide used OD as a function of theserum tested for ELISA P1 P2 P3 P4 P5 P6 P7 P8 no peptide 0.05 0.08 0.070.06 0.06 0.06 0.05 0.04 HHV-8 peptide 0.13 0.16 0.17 0.15 0.15 0.140.16 0.14 H7GB 129-152 1.11 0.56 0.96 0.60 0.69 1.01 0.64 0.88

EXAMPLE 3 Test in an ELISA System Using H7GB 129-152 Peptide fromPositive HHV-7 Serums Towards H7GB 129-152 Peptide, After Adsorption ofSerums onto Different Infected Cell Extracts

[0058] The eight human serums P1 to P8 were adsorbed with differentextracts from cells infected or otherwise prior to being tested usingELISA towards the H7GB 129-152 peptide under pre-established conditions.The results are expressed as a percentage reduction compared with thesignal obtained in the absence of any pre-adsorption (see Example 2).The results summarized below indicate that only pre-adsorption withcells expressing HHV-7 gB could significantly reduce the signal.preadsorption percentage reduction in OD (%) cells infection P1 P2 P3 P4P5 P6 P7 P8 SupT1 none 5 29 0 11 20 0 11 17 SupT1 HHV-7 40 58 56 52 5043 40 56 Sf21 none 11 22 0 0 17 0 0 0 Sf21 Baculovirus expressing 46 6630 26 57 26 60 42 HHV-7 gB MT4 none 20 2 4 10 13 7 11 0 MT4 HHV-6 11 011 3 19 6 0 0 FH none 18 0 13 0 9 13 0 6 FH CMV 20 5 8 0 11 2 3 0

EXAMPLE 4 Test in an ELISA System Using H7GB 129-152 Peptide from SixSeronegative HHV-7 Serums

[0059] Six reference serums designated N1 to N6 which were seronegativefor HHV-7 but had a very high titer of anti-HHV-6 antibodies (>1280)were tested. The results show a low reactivity to the peptide. As forthe seropositive serums, they also show a variability, expressed in theform of a coefficient of variability (CV), which was sufficiently low toenvisage development of a routine ELISA test. coefficient of variability(%) test serum mean OD SD intra-test inter-test N1 0.20 0.02 9.5 8.8 N20.16 0.02 8.3 13.8 N3 0.18 0.01 3.3 3.6 N4 0.17 0.02 11.0 11.0 N5 0.180.01 13.2 4.8 N6 0.16 0.07 44.7 47.0

EXAMPLE 5 Inhibiting Action of Soluble Peptide, Previously Brought intoContact with Serums, on ELISA Reactivity

[0060] Positive serums P1 to P8 were pre-incubated in the presence ofsoluble H7GB 129-152 at two different concentrations then tested usingELISA. The reduction in the signal with respect to the same nonincubated serums results from the competition exerted by the solublepeptide towards anti-HHV-7 antibodies. concentration of H7GB 129-152percentage OD reduction (%) during pre-incubation (μg/ml) P1 P2 P3 P4 P5P6 P7 P8  5 27 30 32 48 14 23 37 24 50 75 45 66 61 70 67 63 61

REFERENCES

[0061] Franti M, Aubin J T, Poirel L, Gautheret-Dejean A, Candotti D,Huraux J M and Agut H. Definition and distribution analysis ofglycoprotein B gene alleles of human herpesvirus 7. J Virol 1998; 72:8725-30.

[0062] Franti M, Aubin J T, Gautheret-Dejean A, Malet I, Cahour A,Hufaux J M and Agut H. Preferential associations of alleles of threedistinct genes argue for the existence of two prototype variants ofhuman herpesvirus 7. J Virol 1999, 73: 9655-58.

[0063] Nicholas J. Determination and analysis of the complete nucleotidesequence of human herpesvirus 7. J Virol 1996: 70: 5975-89.

[0064] Megaw A G, Rapaport D, Avidor B, Frenkel N, Davison A J. The DNAsequence of the RK stain of human herpesvirus 7. Virology 1998; 244:119-32.

1 7 1 24 PRT Human Herpesvirus 7 1 Leu Ser Ser Ile Ser Val Lys Arg SerGlu Glu Glu Glu Tyr Val Ala 1 5 10 15 Tyr His Lys Asp Glu Tyr Val Asn 202 6 PRT Human Herpesvirus 7 2 Arg Ser Glu Glu Glu Glu 1 5 3 12 PRT HumanHerpesvirus 7 3 Ser Val Lys Arg Ser Glu Glu Glu Glu Tyr Val Ala 1 5 10 451 PRT HUMAN HERPESVIRUS 7 4 Pro Ile Glu Glu Val His Met Val Asn Thr GluAla Arg Cys Leu Ser 1 5 10 15 Ser Ile Ser Val Lys Arg Ser Glu Glu GluGlu Tyr Val Ala Tyr His 20 25 30 Lys Asp Glu Tyr Val Asn Lys Thr Leu AspLeu Ile Pro Leu Asn Phe 35 40 45 Lys Ser Asp 50 5 51 PRT HUMANHERPESVIRUS 6A 5 Pro Val Tyr Glu Ala Asn Leu Val Asn Ser His Ala Gln CysTyr Ser 1 5 10 15 Ala Val Ala Met Lys Arg Pro Asp Gly Thr Val Phe SerAla Phe His 20 25 30 Glu Asp Asn Asn Lys Asn Asn Thr Leu Asn Leu Phe ProLeu Asn Phe 35 40 45 Lys Ser Ile 50 6 51 PRT HUMAN HERPESVIRUS 6B 6 ProMet Tyr Glu Ala Asn Leu Val Asn Ser Arg Ala Gln Cys Tyr Ser 1 5 10 15Ala Val Ala Ile Lys Arg Pro Asp Gly Thr Val Phe Ser Ala Tyr His 20 25 30Glu Asp Asn Asn Lys Asn Glu Thr Leu Glu Leu Phe Pro Leu Asn Phe 35 40 45Lys Ser Val 50 7 50 PRT cytomegalovirus (CMV) 7 Pro Met Trp Glu Ile HisHis Ile Asn Lys Phe Ala Gln Cys Tyr Ser 1 5 10 15 Ser Tyr Ser Arg ValIle Gly Gly Thr Val Phe Val Ala Tyr His Arg 20 25 30 Asp Ser Tyr Glu AsnLys Thr Met Gln Leu Ile Pro Asp Asp Tyr Ser 35 40 45 Asn Thr 50

1. An immunogenic peptide comprising at least six consecutive aminoacids from a hydrophilic region of the glycoprotein B (gB) of humanherpesvirus 7 (HHV-7) and reacting in a specific manner with antibodiesdirected against HHV-7.
 2. A peptide according to claim 1, characterizedin that the amino acid sequence of the gB present in the peptides of theinvention derive from the N-terminal region of said protein.
 3. Apeptide according to claim 1 or claim 2, characterized in that itcomprises the sequence Arg-Ser-Glu-Glu-Glu-Glu.
 4. A peptide accordingto any one of claims 1 to 3, characterized in that it comprises thesequence Ser-Val-Lys-Arg-Ser-Glu-Glu-Glu-Glu-Tyr-Val-Ala; modified, ifappropriate, by conservative modification(s) that do not modify theimmunological reactivity of said peptide.
 5. A peptide according to anyone of claims 1 to 4, comprising 15 to 25 amino acids.
 6. A peptideaccording to any one of claims 1 to 5, corresponding to amino acids 129to 152 of gB and defined by the peptide sequence:Leu-Ser-Ser-Ile-Ser-Val-Lys-Arg-Ser-Glu-Glu-Glu-Glu-Tyr-Val-Ala-Tyr-His-Lys-Asp-Glu-Tyr-Val-Asnmodified, if appropriate, by conservative substitution(s) which do notmodify the immunological reactivity of said peptide.
 7. A peptideaccording to any one of claims 1 to 6, further comprising one or moreterminal amino acids that are heterologous to gB.
 8. A kit enablingspecific diagnosis of HHV-7, comprising a peptide according to any oneof claims 1 to
 7. 9. A diagnostic kit according to claim 8,characterized in that said peptide is fixed to a support.
 10. Adiagnostic kit according to claim 8 or claim 9, further comprising adetectable antibody directed against one or more classes of humanimmunoglobulins.
 11. A diagnostic kit according to claim 10, in whichthe detectable antibody is radiolabelled, fluorescent or bound to anenzyme.
 12. A diagnostic kit according to claim 11, in which thedetectable antibody is bound to an enzyme and further comprises asubstrate for said enzyme that can produce a visually detectable result.13. A diagnostic kit according to any one of claims 8 to 12, furtherallowing serological diagnosis of one or more other β herpesviruses. 14.A method for the serological detection of HHV-7 in a biological sample,comprising a step for bringing said biological sample into contact witha peptide according to any one of claims 1 to 7, and a step fordetermining bonding of the peptide with any antibodies that may bepresent in the sample.
 15. A method according to claim 14, in which thestep for determining bonding of the peptide with any antibodies that maybe present in the sample is carried out using an ELISA test, bychemiluminescence, by fixing onto a micro- or macro-array type support,by immunofluorescence, by radio-immuno-labelling, by agglutination or byhaemagglutination.
 16. An immunogenic preparation for encouraging animmune response against HHV-7, characterized in that it comprises atleast one peptide according to any one of claims 1 to
 7. 17. Use of apeptide according to any one of claims 1 to 7, in preparing acomposition for the serological detection of HHV-7, for diagnosing HHV-7in a subject, or for stimulating an immune response directed againstHHV-7 in a subject.